title: Acetylation of MnSOD directs enzymatic activity responding to cellular nutrient status or oxidative stress.
abstract: A fundamental observation in biology is that mitochondrial function, as measured by increased reactive oxygen species (ROS), changes significantly with age, suggesting a potential mechanistic link between the cellular processes governing longevity and mitochondrial metabolism homeostasis. In addition, it is well established that altered ROS levels are observed in multiple age-related illnesses including carcinogenesis, neurodegenerative, fatty liver, insulin resistance, and cardiac disease, to name just a few. Manganese superoxide dismutase (MnSOD) is the primary mitochondrial ROS scavenging enzyme that converts superoxide to hydrogen peroxide, which is subsequently converted to water by catalase and other peroxidases. It has recently been shown that MnSOD enzymatic activity is regulated by the reversible acetylation of specific, evolutionarily conserved lysine(s) in the protein. These results, suggest for the first time, that the mitochondria contain bidirectional post-translational signaling networks, similar to that observed in the cytoplasm and nucleus, and that changes in lysine acetylation alter MnSOD enzymatic activity. In addition, these new results demonstrate that the mitochondrial anti-aging or fidelity / sensing protein, SIRT3, responds to changes in mitochondrial nutrient and/or redox status to alter the enzymatic activity of specific downstream targets, including MnSOD that adjusts and/or maintains ROS levels as well as metabolic homeostatic poise.
authors.affiliation: Departments of Cancer Biology, Pediatrics, and Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Ozkan
authors.initials: O
authors.lastname: Ozden
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Coleman
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Spitz
authors.forename: David
authors.initials: D
authors.lastname: Gius
mesh_terms: D000107:Acetylation; D000818:Animals; D004734:Energy Metabolism; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D056566:Sirtuin 3